Evidence-based medicine and evidence-based laboratory medicineThe development of evidence-based medicine (EBM) is just as important to laboratory medicine and POCT as to medical practice in its broadest context. The generally accepted definition of evidence-based medicine is that given by Sackett etal, namely “the conscientious, explicit and judicious use of current best evidence in making decisions about the care of patients”.66 As discussed by Price, “this definition can readily be applied to laboratory medicine because:
- a request for a diagnostic test represents part of the decision-making process
- the relevance of the test to the clinical situation at hand and its fitness for purpose
- of the need for a critical appraisal of the evidence in terms of testing quality
- the continuing evolution of evidence, particularly of new tests or testing procedures requires continuous evaluation.”67
The application of evidence-based medicine also provides an assessment of the most cost- effective manner for treating the average patient in order to obtain the best health outcome. Individual patients however, may vary considerably from this average. This deviation and the initiation of appropriate treatment is where clinical judgment is required.
The application of evidence-based medicine to diagnostic laboratory testing is now universally accepted by professional colleges and associations in the medical and clinical sciences. Procedural guidelines provided by medical colleges are now largely described as “evidence-based” and EBM has become well established as a component of both undergraduate and postgraduate medical education. In the same manner, evidence-based laboratory medicine (EBLM) is an essential part of modern diagnostic laboratory practice as reviewed by Price,68 Hawkins,69 Oosterhuis etal,70, Christenson71 and Christenson etal.72
The place of EBM in Australian medical literature also appears well established as evidenced by the statement that the Medical Journal of Australia (MJA) is second only to the British Medical Journal (BMJ) “in publishing the largest number of references indexed under the term “evidence-based medicine” in English-language journals.”3
Evidence-based laboratory medicine and POCTIn addition to traditional laboratory based testing, evidence-based procedures have also been applied to POCT by The National Academy of Clinical Biochemistry (NACB) with an extensive set of practice guidelines, Evidence-based practice for point-of-care testing.61
However, if applying existing laboratory evidence to POCT procedures, it is important to confirm that:
- such evidence matches the patient or patient group being considered
- the accuracy and precision of the POCT system is appropriate for the proposed circumstances (see comments with regard to “fitness for purpose”, below)
- conclusions derived using high quality data are not transferred to situations in which the analytical results are provided at an inferior level of testing (as discussed previously)
- there is good concordance of the proposed POCT results with established laboratory procedures (such that reference intervals and action limits in current use are applicable)
- clinical practice guidelines (such as the WHO and/or NHMRC guidelines for the diagnosis and management of diabetes mellitus) are still applicable.
The importance of these cautions is clearly shown by the World Health Organisation (WHO) criteria for the diagnosis of diabetes mellitus,72 which provide the diagnostic criteria for diabetes currently used within Australia.73 The recommended diagnostic criteria for diabetes mellitus use plasma glucose measured in an accredited laboratory, not whole blood glucose measured with a POCT device. The revised evidence-based Guidelines and recommendations for laboratory analysis in the diagnosis and management of diabetes mellitus from the NACB make this point even more strongly (Chapter 3, Glucose meters.
- “A. . Diagnosis/screening. The glucose-based criteria for the diagnosis of diabetes are based upon outcome data (the risk of micro- and macro- vascular disease) correlated with plasma glucose concentrations (both fasting and 2 h after a glucose load), assayed in an accredited laboratory. Whole blood is used in portable meters. Although most portable meters have been programmed to report a plasma glucose concentration, the imprecision of the current meters precludes their use in the diagnosis of diabetes. Similarly, screening by portable meters, although attractive because of convenience, ease and accessibility, would generate many false positives and false negatives.”75
- to minimize glycolysis, “an effective glycolysis inhibitor such as citrate buffer should be used”
- “on the basis of biological variation, glucose measurement should have an analytical imprecision £ 2.9%, a bias £ 2.2% and a total error £ 6.9%”
- “there is insufficient published data to support a role for portable meters and skin- prick blood samples in the diagnosis of diabetes or for population screening”
- “laboratories should use only HbA1c methods that are certified by the National Glycohaemoglobin Standardisation Program …”
- “desirable specifications for HbA1c measurement are an intralaboratory CV <2% and an interlaboratory CV <3.5%”.75,76
In addition, a recent systematic review of evidence-based publications describing POCT for HbA1c in the management of diabetes, found “no evidence of the effectiveness of POCT for HbA1c in the management of diabetes”.77
US Food and Drug Administration enquiry into glucose meter performanceStatements critical of the performance and clinical use of glucose meters by the NACB and respected diabetes practitioners,78 have been further highlighted by the recent public enquiry by the US Food and Drug Administration (FDA) into the performance of blood glucose meters.29 Transcripts of the meeting are available (internet link available through reference 29). These transcripts discuss many of the performance aspects of blood glucose meters including issues of concern with regard to quality. They include:
- the analytical quality required for patient monitoring, detection of hypoglycemia, and tight glycaemic control
- the clinical requirements for glucose measurement, quality control requirements
- target concentrations for hypoglycemia and glycaemic control
- interferences in the common methodologies employed by blood glucose meters.
An overview of the discussions at the FDA enquiry is provided by Westgard.79 The role of biological variation in determining testing performance and fitness for purpose is discussed below.